Title

Author

Date of Award

Spring 1997

Degree Type

Thesis - Restricted

Degree Name

Master of Science (MS)

Department

Biology

Abstract

Alternative pre-mRNA processing plays an important role in the regulation of gene expression. It modulates the coding capacity of the genome and gives rise to different functional proteins from a single gene. There are several examples of a single gene giving rise to two or more protein products of diverse functions. One of the most interesting is proto-oncogene c-erbAα. In mammals the transcription unit of the erbAα gene encodes 3 mRNAs: erbAαl (αl) which codes for the a-type thyroid hormone receptor (TRαl), erbAα2 (α2) which codes for a functional antagonist of TRαl, a nonhormone-binding protein called TRα2 and lastly erbAα3 which codes for a poorly characterized variant ofTRα2. αl and α2 are identical at their 5' ends but differ in their alternatively processed 3' ends. The expression of αl and α2 mRNA differs in various tissues, reflecting a balance between two mutually exclusive alternative processing events, polyadenylation at the upstream αl-specific site and splicing at the α2-specific exon. Another characteristic feature of the mammalian erbAα genetic locus is it encodes another nuclear receptor, Rev-erb, which is transcribed in the opposite direction from αl and α2. The 3' end of the Rev-erb mRNA is complementary to the 3' end of α2 but not αl mRNA. My project concerns an investigation of post-transcriptional mechanisms which regulate the tissue specific expression of alternatively processed αl and α2 mRNAs. The contribution of individual processing events, α1-specific polyadenylation and α2-specific splicing, which may affect the balance between αl and α2 mRNA, is examined.